Th objective of the proposed research project is the attainment of a better understanding of the molecular mechanisms underlying the protective effect of selenium against chemical carcinogenesis. Initial studies will be conducted to quantitate the effect of dietary selenium (0.5 ppm.) on the incidence of hepatomas in rats fed 2-fluorenylacetamide (FAA). Subsequent experiments will focus on the possible relationship between the anticarcinogenic action of selenium and its function as a component of the enzyme, glutathione peroxidase (GPO). Specifically an attempt will be made to correlate the activity of GPO in the livers of selenium-deficient and selenium-supplemented rats with hepatic malondialdehyde concentrations at various intervals after the addition of FAA to their diets. Other studies will be concerned with the effect of selenium on the metabolism of FAA both in vivo and in vitro. Recently developed high pressure liquid chromatography techniques will be used to separate and quantitate metabolites of FAA excreted in the urine. By similar means the effect of dietary selenium on the metabolism of FAA by hepatic microsomes in vitro will be quantitated. Finally, the effect of selenium on the binding of FAA to hepatic DNA will be investigated. The effect of selenium on the amount of carcinogen initially bound to DNA as well as its effect on the retention of DNA-bound FAA at later intervals will be studied. In conjunction with the studies described above, these investigations should provide new insights into the ability of selenium to protect the liver against potential changes in gene function induced by FAA.